Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery - PubMed (original) (raw)
Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery
Hock Ing Chiu et al. Pharmaceutics. 2020.
Abstract
In this study, fluorescein-labelled wheat germ agglutinin (fWGA)-conjugated disulfide cross-linked sodium alginate nanoparticles were developed to specifically target docetaxel (DTX) to colon cancer cells. Different amounts of 3-mercaptopropionic acid (MPA) were covalently attached to sodium alginate to form thiolated sodium alginate (MPA1-5). These polymers were then self-assembled and air-oxidised to form disulfide cross-linked nanoparticles (MP1-5) under sonication. DTX was successfully loaded into the resulting MP1-5 to form DTX-loaded nanoparticles (DMP1-5). DMP2 had the highest loading efficiency (17.8%), thus was chosen for fWGA surface conjugation to form fWGA-conjugated nanoparticles (fDMP2) with a conjugation efficiency of 14.1%. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses showed spherical nanoparticles, and an in vitro drug release study recorded a cumulative drug release of 48.6%. Dynamic light scattering (DLS) analysis revealed a mean diameter (MD) of 289 nm with a polydispersity index (PDI) of 0.3 and a zeta potential of -2.2 mV for fDMP2. HT-29 human colon cancer cells treated with fDMP2 showed lower viability than that of L929 mouse fibroblast cells. These results indicate that fDMP2 was efficiently taken up by HT-29 cells (29.9%). Fluorescence and confocal imaging analyses also showed possible internalisation of nanoparticles by HT-29 cells. In conclusion, fDMP2 shows promise as a DTX carrier for colon cancer drug delivery.
Keywords: HT-29; disulfide cross-linked nanoparticles; docetaxel; thiolated sodium alginate; wheat germ agglutinin conjugation.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Scheme 1
Synthetic scheme of (A) MPA and (B) assembly process of disulfide cross-linked nanoparticles.
Scheme 1
Synthetic scheme of (A) MPA and (B) assembly process of disulfide cross-linked nanoparticles.
Figure 1
FTIR spectra of sodium alginate, MPA and MP.
Figure 2
1H-NMR spectra of (A) sodium alginate and (B) MPA.
Figure 3
Comparison of the concentrations of thiol between MPA polymers and MP nanoparticles (mean ± SD, n = 3); ** (p < 0.01) and * (p < 0.05) indicate significant differences between the samples.
Figure 4
SEM micrographs of (A) MP2, (C) DMP2, (E) fDMP2; and TEM micrographs of (B) MP2, (D) DMP2, (F) fDMP2.
Figure 5
pH sensitivity profiles of (A) MP1–5 and (B) fMP2 (mean ± SD, n = 3).
Figure 6
In vitro drug release profile of (A) DMP2 and (B) fDMP2 in control media (GSH-free) and in stimulated gastrointestinal media (with GSH) at predetermined pH and time (mean ± SD, n = 3); * (p < 0.05) indicates that significant differences were observed between the samples.
Figure 7
Comparison of effects of fMP2, fDMP2, and DTX on (A) HT-29 cells and (B) L929 cells (mean ± SD, n = 3); the samples with same alphabets a–r indicate significant difference between them, while, sample with * indicates (p < 0.05) compared to untreated cells.
Figure 8
Cellular uptake profile of fDMP2 by HT-29 cells as a function of (A) incubation time and (B) concentration over an incubation period of 2 h (mean ± SD, n = 3); ** indicates p < 0.01 between the two time intervals.
Figure 9
Cellular uptake of fDMP2 by HT-29 cells (2 h) under 40,000 × magnifications illustrated by fluorescence microscopy.
Figure 10
Colocalisation of clathrin for fDMP2 in HT-29 cells; localisation of clathrin, nucleus, nanoparticles, and the merged image in HT-29 cells.
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